The bioavailabilities of baicalin in water, oil, w/o and o/w emulsion were evaluated in rats. The dissolution rate of baicalin in o/w emulsion was smaller than those of w/o form in dilute hydrochloric acid solution (pH 1.2) and in PBS (pH 6.8). The absorption rate of baicalin from w/o emulsion was smaller than that of o/w emulsion in the different parts of rat intestine of the rats. Following oral administration in rats, the $C_{max}$ of baicalin from water phase, oil phase, o/w wand w/o emulsion were 2.11, 0.61, 1.57, and $1.35\;{\mu}g/ml$, respectively. The relative bioavailability of w/o emusion was 129 % when it was compared with water phase. This result suggests that the improvement of bioavailability for baicalin in w/o emulsion might be practically available.

The captopril matrix tablets composed of polyethylene oxide(PEO) was prepared and administered to beagle dogs. Captopril matrix tablets were prepared using direct compressed method and wet granulation compressed method with various ratios of drug to PEO. The diffusion rate of captopril matrix tablets followed on the Higuchi's diffusion model. With increasing hardness of captopril matrix tablets, release rate was decreased. Each formulation was evaluated by the area under the curve (AUC) and time course of plasma captopril concentration after oral administration to beagle dogs. The $AUC_{0-12}$ were $9.126\;{\mu}g\;h/ml$ and $6.417\;{\mu}g\;h/ml$ for the matrix tablets and conventional tablets, respectively. Therefore, the bioavailability of captopril matrix tablets was greater than that of commercial product. It is suggested that captopril matrix tablets using PEO is a useful sustained release formulation.

Canalicular liver plasma membrane vesicles (cLPM) were prepared according to two different methods (Inoue method and Meier method), and were evaluated for their protein yield, enzyme activity and transport characteristics. No difference was found between the methods in the protein yield (i.e., $0.14{\pm}0.031$ and $0.15{\pm}0.050$ mglg liver for Inoue method and Meier method, respectively). The activity of alkaline phosphatase, a marker enzyme of canalicular membrane, was significantly (P<0.05) higher in the vesicles of Meier method $(3.52{\pm}0.91\;mmol/mg/hr)$than in the vesicles of Inoue method ($2.28{\pm}0.94$ mmol/mg/hr) indicating that more purified cLPM were obtained from Meier method compared with Inoue method. ATP-dependent vesicular uptake of taurocholate and tributylmethylammonium (TBuMA) was observed for vesicles of both methods, and the kinetic parameters responsible for the transport were similar between the vesicles of both methods (for example, $V_{max}:$ 9.72 nmol/mg protein/30sec and $K_m:$ 0.63 mM for Inoue method; $V_{max}:$ 10.1 nmol/mg protein/30sec and $K_m:$ 0.70 mM for Meier method). A pH gradient dependent counter transport of TBuMA was also observed for both vesicles with similar kinetic characteristics. Either the uptake of taurocholate in the absence of ATP or that of TBuMA in the absence of pH gradient, which may represent passive diffusion of respective compound into the vesicles, was more rapid for the vesicles of Meier method than for the vesicles of Inoue method. For example, passive diffusion rate constants $(K_d)$ for TBuMA uptake into the vesicles were 0.00030 and 0.00052\;{\mu}l/mg$ protein/min for the vesicles of Inoue method and Meier method, respectively. It may indicate that more leaky vesicles are obtained form the Meier method compared with the Inoue method. These aspects together with the time necessary to prepare the vesicles (i.e., 8 hr for Inoue method and 23 hr for Meier method) should be considered before selecting an appropriate method for the preparation of cLPM.

Semi-solid poly(ortho esters) (POE) were prepared to provide bioerodible carriers for sustained drug delivery systems of naloxone (NLX) in the treatment of narcotic addiction. As the POE have viscous behavior at room temperature, a significant advantage of this polymer is that it can be injected without any surgical intervention. The POE was synthesized by a transesterification reaction between 1,2,6-hexanetriol and trimethyl orthoacetate, and the structure of the polymer was confirmed by IR. The in vitro release of the drug from POE was studied. The release rate of NLX decreased with increasing intrinsic viscosities of the polymer. In vivo biocompatibility studies were carried out in rats with NLX loaded POE. Histopathological analysis showed that NLX implants are well-tolerated by rats when used subcutaneously. Pharmacokinetic studies of POE-NLX implants of two different viscosities were carried out in rabbits. In all cases, plasma concentrations of NLX were maintained over 1 ng/ml for at least 168 hours, but initial burst effect was observed. Mean residence time(MRT) was found to depend on the viscosity of the polymer.

Aceclofenac is an non-steroidal antiinflammatory drug which has been used in the treatment of rheumatoidal rthritis and osteo-arthritis. In order to decrease the gastric ulcerogenic effects and contol the plasma level of aceclofenac, we have developed the transdermal delivery system of aceclofenac plaster, which were formulated employing matrix polymers of acrylates and penetration-enhancers such as $Lauroglycol^{\circledR}$, $Transcutol^{\circledR}$, oleic acid and linoleic acid. Using Franz diffusion cells mounted with a rat skin, transdermal penetration characteristics of the formulations were evaluated by the HPLC assay of aceclofenac and diclofenac, an active metabolite, in the receptor compartment of pH 7.2 phosphate buffered solution. Skin penetration was increased when the content of aceclofenac increased, showing the flux $(J,\;{\mu}g/cm^2/hr)$ of 0.37 and 2.50 for 2% and 6.75% of the content, respectively. The flux$(J,\;{\mu}g/cm^2/hr)$ from plasters made of $Durotak^{\circledR}$ 87-2074, $Durotak^{\circledR}$ 87-2510 and $Durotak^{\circledR}$ 87-2097 were 2.50, 2.77 and 4.39, respectively. $Durotak^{\circledR}$ 87-2074 showed the lowest penetration due to the carboxylic acid group in the polymer, which might form a strong hydrogen bonding with a secondary amine of aceclofenac. Although both $Durotak^{\circledR}$ 87-2510 and $Durotak^{\circledR}$ 87-2097 are amine-resistant adhesives, $Durotak^{\circledR}$ 872510 showed lower penetration than $Durotak^{\circledR}$ 87-2097 because of the hydroxyl group in $Durotak^{\circledR}$ 87-2510, which might form a weak hydrogen bonding with aceclofenac. These results reveal that the functional group in acrylic polymers would greatly affect the release of aceclofenac from the matrix, which is the rate-limiting step in the penetration of aceclofenac through rat skins. The penetration of aceclofenac from plasters using different penetration-enhancers increased in the following order: Transcutol < linoleic acid < oleic acid. And the flux from the plasters containing oleic acid as a penetrationenhancer was 2.22 times greater than that of creams, which suggest that a newly deveolped aceclofenac plaster could be used in the treatment of rheumatoidal arthritis and osteo-arthritis as an advanced transdermal delivery system.

ABSTRACT-A self-microemulsifying drug delivery system (SMEDDS) was developed to enhance the solubility and dissolution rate of poorly water soluble drug, biphenyl dimethyl dicarboxylate, DDB. The system was optimized by evaluating the solubility of DDB and the microemulsion existence range after the preparation of microemulsions with varying compositions of triacetin and surfactant-cosurfactant mixtures (Labrasol as surfactant (S) and the combination of Transcutol, Cremophor RH 40 and Plurol oleique as cosurfactant (CoS)). SMEDDS in this study markedly improved the solubility of DDB in water up to 10 mg/ml and the size of the o/w microemulsion droplets measured by dynamic light scattering showed a narrow monodisperse size distribution with an average diameter less than 50 nm. The microemulsion existing range is increased proportional to the ratio of S/CoS, however, it decreased remarkably as the oil content was more than 20%. In vitro dissolution study of SMEDDS showed a significantly increased dissolution rate of DDB in water (> 12 fold over DDB powder), and SMEDDS also had significantly greater permeability of DDB in Caco-2 cell compared to powders.

Gastrodia elata (GE) is an oriental medicinal herb which has been used traditionally for the treatment of various brain diseases including convulsion and epilepsy. The purpose of this study was to determine pharmacokinetic parameters of 4-hydroxy-3-methoxybenzaldehyde (HMBA) and p-hydroxybenzaldehyde (PHBA), constituents of GE, in rats. Male rats were cannulated in the femoral vein, femoral artery, bile duct and ureter. They received a single i.v. bolus dose of either HMBA or PHBA through the femoral vein. The concentration of HMBA or PHBA in plasma, bile and urine samples were analyzed by reversed-phase HPLC. HMBA and PHBA have very short half-lives, i.e. 4.03 and 2.26 minutes respectively. Most of HMBA and PHBA were thought to be eliminated through metabolism as the metabolized fraction approaches unity. Derivatives of HMBA or PHBA with longer biological half-lives should be designed to develop better anticonvulsants and more complete qualitative and quantitative understanding of the overall pharmacokinetic fate of these compounds awaits further investigation.

We previously showed that a methanol extract of Paeoniae radix decreased total cholesterol level in rats with hyperlipidemia. In order to isolate the active ingredient(s), the methanol extract of Paeoniae radix was fractionated with chloroform/methanol(4:1) solution and isolate into soluble part and insoluble part of the the methanol extract. Above two parts were tested on the experimentally induced hypercholesterolemia in rats for the lowering effect of serum lipoprotein contents. Hyperlipidemia was induced on male Wistar rats by feeding high choleserol diet for 7 days. After oral administration of above samples for 4 weeks, serum lipid profile was verified on these rats by measuring total cholesterol, triglyceride, high density lipoprotein cholesterol and low density lipoprotein cholesterol. The chloroform/methanol(4:1) soluble part and insolule part showed lowering activity of total cholesterol level and triglyceride level at 4 week point significantly(p<0.01 and p<0.05) compare with the control group and the soluble part was more effective.

Bioequivalence of two terazosin tablets, the $Hytrine^{TM}$ (Il-Yang Pharmaceutical Co., Ltd.) and the $Hytrine^{TM}$ (Daewon Pharmaceutical Co., Ltd.), was evaluated according to the guideline of KFDA. Sixteen normal male volunteers $(21{\sim}30\;years\;old)$ were divided into two groups and a randomized $2{\times}2$ cross-over study was employed. After one tablet containing 2 mg of terazosin was orally administered, blood was taken at predetermined time intervals and the concentration of terazosin in serum was determined with a HPLC method using spectrofluorometric detector. The pharmacokinetic parameters $(AUC_t,\;C_{max}\;and\;T_{max})$ were calculated and ANOVA was utilized for the statistical analysis of the parameters. The results showed that the differences in $AUC_t$ $C_{max}$ and $T_{max}$ between two tablets were 6.02%,3.44% and -3.67%, respectively. The powers $(1-{\beta})$ for $AUC_t$, $C_{max}$ and $T_{max}$ were 98.05%, 98.34% and 29.81 %, respectively. Detectable differences $({\Delta})$ and confidence intervals were all less than ${\pm}20%$ except $T_{max}$. $AUC_t$ and $C_{max}$ met the criteria of KFDA for bioequivalence, indicating that $Terasin^{TM}$ tablet is bioequivalent to $Hytrine^{TM}$ tablet.

A bioequivalence study of the $Kerola^{\circledR}$ intramuscular injections (Dongkwang Pharmaceutical Co., Korea) to the $Tarasyn^{\circledR}$ intramuscular injections (Roche Co., Korea), formulations of ketorolac tromethamine (KTR), was conducted. Sixteen healthy Korean male subjects were received each formulation at the dose of 30 mg as KTR in a $2{\times}2$ crossover study. There was an one-week washout period between the doses. Plasma concentrations of KTR were monitored by a HPLC method. AUC was calculated by the linear trapezoidal method. $C_{max}$ and $T_{max}$ were compiled from the plasma drug concentration-time data. Analysis of variance (ANOVA) revealed that there are no differences in AUC, $C_{max}$ and $T_{max}$ between the formulations. The differences between the formulations in these parameters were all far less than 20% (i.e., 3.65, 2.59 and 4.35% for AUC, $C_{max}$ and $T_{max}$ respectively). Minimum detectable differences (%) at ${\alpha}=0.1$ and $1-{\beta}=0.8$ were 12.87, 13.44, 20.62%, for AUC, $C_{max}$ and $T_{max}$, respectively. The 90% confidence intervals for these parameters were also within 20%. These results satisfy the bioequivalence criteria of the Korea Food and Drug Administration (KFDA) guidelines (No. 1998-86). Therefore, these results indicate that the two formulations of KTR are bioequivalent.